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Investigation of species differences in isobutene (2-methylpropene) metabolism between mice and rats

Research paper by G. A. Csanády, D. Freise, B. Denk, J. G. Filser, M. Cornet, V. Rogiers, R. J. Laib

Indexed on: 01 Feb '91Published on: 01 Feb '91Published in: Archives of Toxicology



Abstract

Metabolism of isobutene (2-methylpropene) in rats (Sprague Dawley) and mice (B6C3F1) follows kinetics according to Michaelis-Menten. The maximal metabolic elimination rates are 340 μmol/kg/h for rats and 560 μmol/kg/h for mice. The atmospheric concentration at which Vmax/2 is reached is 1200 ppm for rats and 1800 ppm for mice. At steady state, below atmospheric concentrations of about 500 ppm the rate of metabolism of isobutene is direct proportional to its concentration. 1,1-Dimethyloxirane is formed as a primary reactive intermediate during metabolism of isobutene in rats and can be detected in the exhaled air of the animals. Under conditions of saturation of isobutene metabolism the concentration of 1,1-dimethyloxirane in the atmosphere of a closed exposure system is only about 1/15 of that observed for ethene oxide and about 1/100 of that observed for 1,2-epoxy-3-butene as intermediates in the metabolism of ethene or 1,3-butadiene.